Roflumilast Plus Alogliptin Proof-of-Mechanism Study in Type2 Diabetes

NCT01664624 | Completed Phase 1 Results

• 2 other identifiers: ROF-T2D_107U1111-1128-6945
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to assess the effect of roflumilast plus alogliptin on glucagon-like peptide-1 (GLP-1) and glucose levels in patients with type 2 diabetes.

Conditions

Type 2 Diabetes

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Postprandial Area Under the Curve From Time 0 to 8 Hours (AUC[0-8]) for Active Glucagon-like Peptide-1

  The concentration of glucagon-like peptide-1 (GLP-1) in blood before and up to 8 hours after eating (postprandial) was plotted and the area under the curve calculated using the linear trapezoidal rule at Baseline and on Day 11. Least squares means of the change from Baseline to Day 11 were obtained using an analysis of covariance (ANCOVA) model with treatment as fixed effect, and Baseline postprandial AUC (0-8) of active GLP-1 as a continuous covariate.

  Baseline and Day 11; samples were taken at -15 min and -5 min (pre-meal), and 15 min, 30 min, and 1, 2, 3, 4, 6, and 8 hours (post-meal).

Secondary Outcomes (5)

• Change From Baseline in AUC(0-8) of Postprandial Plasma Glucose

  Baseline and Day 11 at -15 min and -5 min (pre-meal), and 15 min, 30 min, and 1, 2, 3, 4, 6, and 8 hours (post-meal).

• Change From Baseline in Postprandial AUC(0-8) of C-peptide

  Baseline and Day 11; samples were taken at -15 min and -5 min (pre-meal), and 15 min, 30 min, and 1, 2, 3, 4, 6, and 8 hours (post-meal).

• Change From Baseline in Postprandial AUC(0-8) of Insulin

  Baseline and Day 11; samples were taken at -15 min and -5 min (pre-meal), and 15 min, 30 min, and 1, 2, 3, 4, 6, and 8 hours (post-meal).

• Change From Baseline to Day 11 in AUC(0-8) of Appetite Sensation

  At Baseline and Day 11, every 30 minutes, starting 1 hour before eating until 8 hour after the meal.

• Change From Baseline to Day 11 in 24-hour Average Plasma Glucose

  Baseline (Day -1) and Day 11, from 12 AM through 24 hours.

Study Arms (4)

Roflumilast + alogliptin

EXPERIMENTAL

Roflumilast 500 μg, tablets, orally and alogliptin 25 mg, tablets, orally, once a day for 11 days.

Drug: Roflumilast; Drug: Alogliptin

Alogliptin alone

EXPERIMENTAL

Placebo to roflumilast, tablets, orally and alogliptin, 25 mg, tablets, orally, once a day for 11 days.

Drug: Alogliptin; Drug: Placebo to roflumilast

Roflumilast alone

EXPERIMENTAL

Roflumilast 500 μg, tablets, orally and placebo to alogliptin, tablets, orally, once a day, for 11 days.

Drug: Roflumilast; Drug: Placebo to alogliptin

Exenatide

ACTIVE COMPARATOR

Exenatide 5 μg subcutaneous injection twice a day for 11 days.

Drug: Exenatide

Interventions

Roflumilast DRUG

Roflumilast tablets

Also known as: Daxas, Daliresp

Roflumilast + alogliptin; Roflumilast alone

Alogliptin DRUG

Alogliptin tablets

Also known as: Nesina

Alogliptin alone; Roflumilast + alogliptin

Exenatide DRUG

Exenatide solution

Also known as: Byetta, Bydureon

Exenatide

Placebo to roflumilast DRUG

Placebo-matching roflumilast tablets

Alogliptin alone

Placebo to alogliptin DRUG

Placebo-matching alogliptin tablets

Roflumilast alone

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, aged 18 to 80 years, inclusive, at the time of dosing on Day 1.
• Has an historical diagnosis of type 2 diabetes mellitus (T2DM) disease.
• Has a documented history of a diet and exercise plan and is receiving metformin as monotherapy at a stable dose for at least 8 weeks prior to Screening; has no chronic use (\>7 days) of any other antidiabetic therapy within the 8 weeks prior to Screening.
• Has inadequate glycemic control at Screening, as evidenced by HbA1c (glycosylated hemoglobin) level between 7.0% and 10.0%, inclusive.
• Has a body mass index (BMI) of ≥23.0 kg/m\^2 and ≤45.0 kg/m\^2, at Screening.
• A female of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study and for 30 days after the last dose of study drug.
• A male who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 30 days after last dose of study drug
• In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
• The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.

You may not qualify if:

• Has a history of type 1 diabetes.
• Has a history of acute metabolic diabetic complications.
• Has has abnormal Screening or Check-in (Day -2) laboratory values that suggest a clinically significant underlying disease (eg, active liver disease or jaundice) or participant with the following laboratory abnormalities: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \>3 × upper limit of normal (ULN).
• Has a history of diabetic gastroparesis or history of gastric bypass surgery.
• Has a history of coronary angioplasty, coronary stent placement, coronary bypass surgery, or myocardial infarction within 6 months prior to Screening.
• Has New York Heart Association heart failure of Class (III-IV) regardless of therapy.
• Has a supine blood pressure \>150 mm Hg for systolic or \>90 mm Hg for diastolic, confirmed on repeat testing within a maximum of 5 minutes, at Screening and Check-in (Day -2).
• Has presence or history of neuropsychiatric disorder (eg, psychosis, psychotic disorders, depression associated with suicidal thinking, suicidal ideation or behavior).
• Has a history of drug abuse (defined as illicit drug use) or a history of alcohol abuse (defined as regular or daily consumption of more than 4 alcoholic drinks per day) within the past 2 years or is unwilling to agree to abstain from alcohol and drugs throughout the study.
• Has a hemoglobin ≤120 g/L for men and ≤100 g/L for women.
• Has a history of clinically significant allergies or idiosyncrasies to roflumilast, alogliptin and exenatide or any inactive ingredient(s) of these products, eg, rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, glucose-galactose malabsorption or phenylketonuria.
• Has received alogliptin or roflumilast in a previous clinical study or as a therapeutic agent within 2 months prior to Screening, or is taking prescription roflumilast for chronic obstructive pulmonary disease (COPD), or has received any other investigational compound within 30 days prior to the first dose of study medication, or is participating or plans to participate in any other clinical trial during this study.
• If female, is pregnant or lactating or intending to become pregnant before, during, or within 30 days after last dose; or intending to donate ova during such time period.
• If male, intends to donate sperm during the course of the study or for 30 days after last dose of study medication.
• Is an immediate family member, study site employee, or in a dependent relationship with a study site employee who is involved in the conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (2)

Unknown Facility

Chula Vista, California, United States

Location

Unknown Facility

Orlando, Florida, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Roflumilast; alogliptin; Exenatide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors

Results Point of Contact

• Title: AstraZeneca Clinical Study Information Center
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• AstraZeneca AstraZeneca

  AstraZeneca

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2012
• First Posted: August 14, 2012
• Study Start: July 1, 2012
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: February 1, 2017
• Results First Posted: February 20, 2014

Record last verified: 2016-09

Locations

US (2)